This Program Project is designed to answer important unsolved problems about acute myocardial ischemia. One project is concerned with the regulation of transmural distribution of myocardial blood flow in normal hearts or in animal models of human disease, and also evaluates at what levels of flow ischemia occurs. A second project focuses more on what hypoxemia and ischemia do to myocardial performance, and also investigates how different substrates alter the myocardial demand for oxygen. A third project investigates the mechanisms of delayed relaxation caused by ischemia, and does this in isolated perfused heart muscle. The fourth project also studies the mechanism of relaxation of heart muscle in normal and ischemic states, but does this in intact hearts with specific reference to the ways in which intrapleural and intrapericardial pressures affect left ventricular pressure-volume relationships. Finally, the fifth project develops an improved technology for the use of microspheres to measure regional blood flow, a technique that is essential for two of the projects. It is the combination of these interrelated projects that should improve our knowledge of the causes and treatment of myocardial ischemia.